Move over, Roche: AstraZeneca and Daiichi's Enhertu snags FDA nod for earlier breast cancer use

AstraZeneca and Daiichi Sankyo have officially escalated the competition in HER2-positive breast cancer treatment.

Thursday, AZ and Daiichi said the FDA has approved their rising star Enhertu for patients with unresectable or metastatic HER2-positive breast cancer after one prior anti-HER2 therapy, either in the metastatic phase or in the early-stage setting.

The go-ahead didn’t come as a surprise. After a monster showing against Roche’s Kadcyla in a clinical trial, Enhertu has largely been viewed as the new standard of care for second-line HER2-positive breast cancer. Analysts at Jefferies have previously said the indication could bring $500 million in worldwide peak sales for Enhertu.

In the phase 3 DESTINY-Breast03 trial, Enhertu cut the risk of disease progression or death by 72% versus Kadcyla in patients previously treated with Roche’s Herceptin and chemotherapy. Both Enhertu and Kadcyla are HER2-directed antibody-drug conjugates.

Enhertu showed a positive trend that it could extend patients’ lives, too. The AZ-Daiichi drug pared down the risk of death by 45% at the interim analysis, though it hasn’t met the prespecified statistical significance bar. After one year, 94.1% of patients on Enhertu were still alive, compared with 85.9% for Kadcyla.

Based on the data, the NCCN Guidelines recently added Enhertu as a second-line therapy for unresectable or metastatic HER2-positive disease with category 1 recommendation, the highest level.

The FDA doled out the new green light through its real-time oncology review program, which allows for early regulatory review before completion of a drug application. At the same time, the agency converted Enhertu’s existing accelerated approval in third- and later-line breast cancer into a full nod.

The FDA also evaluated Enhertu in collaboration with foreign regulators in Australia, Brazil, Canada, Israel and Switzerland under Project Orbis.

Although Kadcyla may feel the pressure, the Roche drug has another indication as an adjuvant treatment for patients with HER2-positive early breast cancer after surgery. That use has been driving its growth lately.

But it’s not just Roche that should worry about Enhertu’s expansion. Seagen also sells small-molecule drug Tukysa in second-line HER2-positive breast cancer, and its clinical data don’t look as impressive as Enhertu’s in their separate trials.

Seagen has projected 2022 Tukysa sales at $325 million, which “reflects concerns regarding the potential entry of Enhertu in the 2L market,” Berenberg analyst Zhiqiang Shu, Ph.D., wrote in a Monday note. He pointed out that Tukysa remains competitive in breast cancer patients with brain metastases.

Meanwhile, AZ and Daiichi have been busy branching Enhertu into new uses. In February, the pair reported positive high-level results for Enhertu in previous treated HER2-low breast cancer, a large patient population that’s estimated to represent up to 55% of all primary breast cancer cases. Two weeks ago, an application for Enhertu in HER2-mutant non-small cell lung cancer was put under FDA priority review, with a decision set for the third quarter.